Gamma‐aminobutyric acid (GABA): a para‐ and/or autocrine hormone in the pituitary

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Furthermore, by acting through pituitary GABAA−, GABAB−, and GABAC receptors, it also plays an important role in the regulation of pituitary function. Although it has generally been assumed that the source of this pituitary GABA is the hypothalamus, here we provide evidence that GABA synthesis also occurs within the pituitary gland itself. Using RT-PCR, in situ hybridization histochemistry, immunohistochemistry, and immunoelectron microscopy, were detected the GABA synthesizing enzyme glutamic acid decarboxylase (GAD 67), the vesicular GABA transporter (VIAAT/VGAT), and GABA in the rat and rhesus monkey pituitary. Although these proteins were found in all of the endocrine cells of the intermediate lobe, we found these proteins in the growth hormone (GH) producing endocrine cells in the anterior lobe only, as well as in a rat GH producing cell line (GH3). In addition, GAD enzyme activity was readily detectable in the rat pituitary and GH3 cells. Many endocrine cells in the anterior pituitary, including GH- cells as well as PRL-, TSH-, ACTH-, and LH/FSH-cells were found to contain GABAA and or GABAB receptors, as shown by double-immunofluorescence staining. Therefore the identification of a novel site of synthesis of GABA within the pituitary, namely POMC-cells of the intermediate lobe and GH cells in the anterior lobe and the presence of pituitary GABA receptors, imply unexpected auto/paracrine actions of the neurotransmitter GABA to occur within the pituitary. These results suggest a new basic mechanism in the regulation of pituitary function by GABA.